Objective ·To investigate the effect of transient receptor potential vanilloid 4 (TRPV4) on traumatic heterotopic ossification around temporomandibular joint (THO-TMJ). Methods ·Eighteen eight-week-old male mice were divided into two groups by simple random sampling. Half right condylar cartilage was removed in every mouse. Nine mice in experimental group was administered TRPV4 blocker [14 mg/(kg·d)] via oral gavage. The same amount of saline was given to nine mice in control group. The skull samples were collected at 14, 30 and 90 d after surgery. The heterotopic ossification was evaluated by H-E staining and Micro CT scan. Three-dimensional reconstruction of the skulls was performed to measure the volume and surface area of condyles. Morphometric index (MI) was applied to indicate the degree of heterotopic ossification in both groups. Results ·H-E staining results showed that active endochondral ossification occurred around the injured condyles in both groups. Micro CT images showed that the tissue density around the condyles in both groups gradually increased in the TMJ area after operation, and then the ectopic bone tissues gradually proliferated outside the condyle, partially connecting to the joint fossa. Scattered osteophytes were seen in the joint space. The trend of TMJ bone fusion was more obvious in the control group. The morphological index of the experimental group (MI=0.15±0.01) was lower than that of the control group (MI=0.18±0.03, P<0.05). Conclusion ·Blocking TRPV4 function can help reduce the formation and progression of THO-TMJ.

Objective ·To investigate the expression of WD 40 repeat protein 43 (WDR43) mRNA in lung adenocarcinoma (LUAD) cells and its correlation with the prognosis of LUAD patients, and analyze the effect of WDR43 on the paclitaxel-resistance of LUAD cells. Methods ·Cancer Therapeutics Response Portal (CTRP) was used to download the correlation coefficient between gene expression and paclitaxel sensitivity of LUAD cells, and the paclitaxel resistance-associated genes were screened. Gene Ontology (GO) function analysis and Kyoto Encyclopedia of Genes and Genome (KEGG) pathway analysis were used to analyze the paclitaxel resistance-associated genes, and WDR43 gene was chosen to perform further study. Human Protein Atlas (HPA) database was used to explore the expression and location of WDR43 protein in LUAD tissues. The cancer genome atlas (TCGA) database was retrieved to analyze the difference of WDR43 mRNA expression in LUAD tissues and normal lung tissues, the mutation of WDR43 in LUAD patients, and the correlation between WDR43 mRNA and clinicopathological factors. CaArray database was used to analyze the relationship between WDR43 mRNA and the prognosis of LUAD patients. Tumor Immune Estimation Resource (TIMER) was used to analyze the relationship between WDR43 expression and the infiltration level of immune cells in LUAD tissues. The expressions of WDR43 gene in LUAD cell lines were analyzed by Cancer Cell Line Encyclopedia (CCLE) database, the WDR43 differential-expressed LUAD cells were constructed and the effect of WDR43 expression on paclitaxel resistance was validated by MTT assay and plate colony formation assay. Results ·WDR43, a paclitaxel sensitivity-related gene, was selected by CTRP. The results of GO function analysis and KEGG pathway analysis showed that WDR43 and other genes were associated with rRNA processing and regulation of cell shape, and were enriched on the pathway such as herpes simplex virus 1 infection and cytosolic DNA-sensing pathway. The analysis results of HPA database showed that WDR43 protein was mainly expressed in the cellular nucleus, cellular cytoplasm and cellular membrane of LUAD tissues. The analysis results of TCGA database showed that the expression of WDR43 mRNA in LUAD tissues was higher than that in normal lung tissues (P=0.000), the expression in cancer tissues of LUAD smokers was higher than that of non-smokers (P=0.000), and the expression in TP53 mutant patients was also higher than that in TP53 wild-type patients (P=0.000). The analysis results of CaArray database showed that LUAD patients with WDR43 mRNA-high expression had poor prognosis (both P=0.000). The analysis results of TIMER database showed that the expression of WDR43 could promote the infiltration level of neutrophils, CD8⁺ T cells, myeloid-derived suppressor cells and macrophages, and inhibit the infiltration level of CD4⁺ T cells in LUAD tissues. In vitro experiments confirmed that overexpression of WDR43 could enhance the drug resistance of LUAD cells to paclitaxel. Conclusion ·The expression of WDR43 in LUAD tissues is significantly increased and negatively correlated with the prognosis of patients. Overexpression of WDR43 could enhance the paclitaxel resistance of LUAD cells.

Objective ·To explore the phenotype of galectin-9⁺ tumor-associated macrophages (galectin-9⁺TAMs) in muscle-invasive bladder cancer (MIBC). To clarify the regulation of galectin-9⁺TAMs in MIBC microenvironment, and elucidate the mechanism of galectin-9⁺TAMs inhibiting the effector function of CD8⁺T cells and its clinical therapeutic significance in MIBC. Methods ·Phenotype of galectin-9⁺TAMs from MIBC peritumor and tumor tissues was detected by flow cytometry. TCGA (The Cancer Genome Atlas) database was used to sort out the cytokines most relevant to LGALS9 and LGALS9 macrophage gene set. Macrophages were stimulated by recombinant human cytokines in vitro, divided into recombinant human macrophage stimulating factor (rhM-CSF) stimulation group, recombinant human interleukin-16 (rhIL-16) stimulation group and recombinant human interferon-γ (rhIFN-γ) stimulation group. Expression level of galectin-9 among the three groups was verified by flow cytometry. Expression level of galectin-9 on macrophages was detected by flow cytometry after adding M-CSF neutralizing antibody. Effector functions of TAMs were detected by flow cytometry after treating MIBC single cell suspension with anti-galectin-9 antibody. Galectin-9⁺TAMs from peritumor and tumor tissues, and human peripheral blood CD8⁺T cells were sorted and co-cultured in vitro. Effector functions of CD8⁺T cells were detected by flow cytometry. Tumor tissues cultured in vitro were treated with anti-galectin-9 antibody and programmed cell death protein 1 (PD-1) antibody alone or in combination. Tumor cell apoptosis and effector function of CD8⁺T cells were detected by flow cytometry. Results ·Galectin-9⁺TAMs exhibited the phenotype with high expression of human leukocyte antigen DR (HLA-DR), CD86, CD206 and programmed cell death-ligand 1 (PD-L1). Increased IL-10 and transforming growth factor-β (TGF-β) and decreased tumor necrosis factor-α (TNF-α) were secreted by itself. M-CSF, IL-16 and IFN-γ showed the significant difference with LGALS9 and LGALS9 macrophage gene set in TCGA database. Galectin-9 on macrophages increased significantly in rhM-CSF stimulated group and its expression decreased by adding neutralizing antibody. Galectin-9 inhibition switched the activation of TAMs from an immunosuppressive phenotype to a more inflammatory state and PD-L1 on its surface significantly decreased. After cultured in vitro, galectin-9⁺TAMs inhibited the effect of CD8⁺T cells in a partly galectin-9-dependent manner. Compared with applying PD-1 inhibitor alone, percentage of tumor cell apoptosis, the proliferation of CD8⁺T cells and its effector molecules were significantly enhanced or increased in both galectin-9 and PD-1 blockade. Conclusion ·Galectin-9⁺TAMs exhibit an immunosuppressive phenotype and function. Tumor-derived M-CSF induced TAMs to express galectin-9. Galectin-9⁺TAMs inhibit the function of CD8⁺T cells to promote the immune escape of MIBC. Galectin-9 and PD-1 blockade can reactivate the function of CD8⁺T cells more effectively and synergistically.

Objective ·To investigate the effects of different doses of sodium arsenite exposure on human hepatocellular carcinoma cell line LM3, and analyze the underlying potential molecular mechanisms of sodium arsenite-mediated promotion of malignant migration of LM3 cells. Methods ·The model of sodium arsenite exposure was established by continuously culturing LM3 cells in high DMEM glucose medium containing 0, 1 and 10 μmol/L sodium arsenite for 14 weeks. After exposure, the sodium arsenite-containing cell culture medium was discarded, and the cells were allowed to recover in sodium arsenite-free culture medium for one week. Cells from the same batch without sodium arsenite treatment were used as the control group. Subsequently, CCK-8 proliferation assay, Transwell migration assay, and DCFH-DA reactive oxygen species fluorescence probe experiments were performed to verify the effect of chronic sodium arsenite exposure on LM3 cell proliferation, migration, and oxidative stress. Real-time quantitative PCR and Western blotting were performed to elucidate the effect of chronic sodium arsenite exposure on the expression of mRNA and protein related to tumor metastasis in LM3 cells. Results ·Compared with the control group, the sodium arsenite exposure groups (1 μmol/L and 10 μmol/L) had significantly higher reactive oxygen species (ROS) levels (both P>0.05), and sodium arsenite exposure promoted the malignant migration of LM3 cells in a dose-dependent manner (both P>0.05), but sodium arsenite had no significant effect on the proliferation of LM3 cells. Sodium arsenite exposure up-regulated the gene expression levels of vascular endothelial growth factor (VEGF), nicotinamide adenine dinucleotide phosphate oxidases 2 (NOX2), and mitogen-activated protein kinase 8 (MAPK8),and up-regulated the protein expression level of NOX2 and MAPK8. Conclusions ·Sodium arsenite exposure can promote malignant migration and oxidative stress level of LM3 cells, and up-regulate the expression levels of VEGF, NOX2 and MAPK8 genes, suggesting that the mechanism of sodium arsenite promoting malignant migration of LM3 cells may be related to oxidative damage and up-regulation of these genes.

Objective ·To investigate whether the efficacy of tacrolimus (TAC) monotherapy is non-inferior to TAC combined with glucocorticoids (TAC+GC) in the treatment of idiopathic membranous nephropathy (IMN), and evaluate its safety. Methods ·This pilot study was conducted by the Department of Renal Rheumatology and Immunology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine from November 2017 to March 2021. High-risk patients with biopsy-proven IMN were recruited and randomly divided into two groups: TAC monotherapy group only received TAC treatment [an initial dose of 0.050?0.075 mg/(kg·d), maintaining trough blood concentration of 5?10 ng/mL]; TAC combined with GC group (TAC+GC group) received TAC (the same as TAC monotherapy group) combined with prednisone [an initial dose of 0.5 mg/(kg·d) for 8?12 weeks, then tapered until complete withdrawal]. The baseline data of the two groups of patients were collected, and the efficacy indicators and safety indicators of the patients were observed and recorded during the visit. The primary end points of the study were the total remission rate and complete remission rate of proteinuria at 24 weeks of treatment. The secondary end points included the efficacy indicators [24 h urinary protein quantification, serum albumin level and estimated glomerular filtration rate level at 24 weeks of treatment] and the incidence of adverse events (elevated blood glucose, thrombosis and infection). Non-inferiority test was used to compare the total remission rate of proteinuria in the two groups, and the non-inferiority margin was set as -10%. Fisher's precision probability test was used to compare the total remission rate, complete remission rate and adverse events rate of the two groups of patients. Non parametric tests were used to compare the differences of the percentage changes of the efficacy indicators from baseline values after treatment between the two groups. Results ·A total of 36 IMN patients were enrolled, with 18 in TAC monotherapy group and 18 in TAC+GC group. There was no statistically significant difference between the baseline data of the two groups. During the treatment, 1 case was lost in TAC monotherapy group and 3 cases in TAC+GC group. Finally, 36 patients were included in the full analysis set (FAS), 32 patients were included in the per protocol set (PPS), and 36 patients were included in the safety set. The results of non-inferiority test showed that it was not observed that the efficacy of TAC monotherapy was not inferior to that of TAC combined with GC. The risk difference of total remission rate of proteinuria in the two groups was 0 (95%CI -31.9?31.9, P=0.269), and the lower limit was below the non-inferiority margin. In FAS and PPS, there was no significant difference in complete remission rate and total remission rate between the two groups at 24 weeks of treatment, and no significant difference in the percentage changes of the efficacy indicators from baseline values after treatment between the two groups. Ten patients (4 cases in TAC monotherapy group, and 6 cases in TAC+GC group) developed elevated blood glucose over the period of treatment, with no significant difference between the two groups; one patient (TAC+GC group) developed right upper extremity venous thrombosis. Conclusion ·This pilot study finds that the total remission rate and complete remission rate of the two groups are similar at 24 weeks of treatment. The frequency of adverse events in TAC monotherapy group is relatively lower than that in TAC combined with GC group. However, the available data cannot prove that the efficacy of TAC monotherapy is non-inferior to that of TAC combined with GC in the treatment of IMN.

Objective ·To investigate the therapeutic effect of mindfulness-based intervention (MBI) on inpatients with chronic schizophrenia. Methods ·A total of 96 patients with chronic schizophrenia hospitalized in Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine from April to June 2021 were enrolled. They were divided into MBI group (n=48) and control group (n=48) by using random number table. The patients in the MBI group were combined with 5-week MBI on the basis of routine treatment, while the patients in the control group were maintained with routine treatment for 5 weeks. The general data of patients were collected, and the scores of Positive and Negative Syndrome Scale (PANSS), Freiburg Mindfulness Inventory (FMI) and Self-compassion Scale (SCS) were compared between the two groups at baseline and 5 weeks later. Results ·In general data, only the gender difference between the two groups was statistically significant (P=0.041). At baseline, there was no statistically significant difference between the two groups in the total scores of PANSS, FMI and SCS and their factor scores. After 5 weeks, the general psychopathology score of PANSS in the MBI group was lower than that in the control group (P_Bonferroni= 0.044), the total score and acceptance score of FMI were higher than those in the control group (P_Bonferroni=0.018, P_Bonferroni=0.003), and the total score of SCS was also higher than that in the control group (P_Bonferroni=0.000). Conclusion ·MBI can significantly improve mindfulness level and self-compassion ability of hospitalized patients with chronic schizophrenia, and promote the improvement of general psychopathology symptom, which is conducive to rehabilitation.

Objective ·To predict the likelihood of cerebral infarction (CI) in emergency department patients with acute vestibular syndrome (AVS), and to evaluate the clinical value of modified TriAGe+ score. Method ·Patients with AVS admitted to the Emergency Department of Neurology of Shanghai Ninth People's Hospital from January 1, 2021 to August 31, 2021 were collected. There were 128 cases of CI and 127 cases of peripheral vertigo. t test or Mann-Whitney U test was used for inter-group comparison of quantitative data, and χ2 test was used for inter-group comparison of qualitative data. Receiver operating characteristic curve (ROC curve) and area under the curve (AUC) were used to compare the prediction effect of TriAGe+ score, age, blood pressure, clinical features, duration of symptoms and diabetes score (ABCD² score) and posterior circulation ischemia (PCI) score for CI in patients with AVS. Logistic regression was used to study the influence of laboratory indicators on prediction of CI. The TriAGe+ score was then combined with laboratory indicators to formulate improved TriAGe+ score. Results ·In the two groups of variables, the proportion of male, hypertension, history of atrial fibrillation, no history of dizziness or vestibular labyrinth, and dizziness symptom in CI group was higher than that in peripheral vertigo group, and the difference was statistically significant (all P<0.05). Compared with ABCD² score and PCI score, TriAGe+ score had the highest AUC (0.859, 95%CI 0.814?0.904), which was statistically significant (P=0.000). Multivariate Logistic regression results showed that blood glucose level (P=0.007) and blood uric acid level (P=0.008) were independent risk factors for predicting CI. When blood glucose level was greater than 7.95 mmol/L, the best AUC showed a sensitivity of 61.7% and specificity of 66.1%. At the same time, serum uric acid value greater than 382.5 μmol/L showed the best AUC with sensitivity of 35.2% and specificity of 85.0%. When the blood uric acid value is greater than 382.5 μmol/L, it is one point, and when the blood glucose value is greater than 7.95 mmol/L, it is one point, which is added to the TriAGe+ score to form the modified TriAGe+ score. The diagnostic value of the modified TriAGe+ score (AUC=0.872, 95%CI 0.828?0.915) was larger than TriAGe+ score (P=0.007). When the critical value of modified TriAGe+ score was 10.5, the diagnostic accuracy was the best, when the sensitivity was 81.3%, and the specificity was 80.3%. Conclusion ·The modified TriAGe+ score has better clinical application in identifying the occurrence of stroke in patients with acute vestibular syndrome.

Objective ·To evaluate the median effective dose (ED₅₀) and cardiovascular stability of esketamine in combination with lidocaine for pediatric patients undergoing circumcision. Methods ·Children aged 3?7 years selected for circumcision between April and June 2021 in Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicinewere enrolled in this study. All children enrolled were administrated 0.5% lidocaine 1.5 mg/kg intravenously after anesthesia was induced by esketamine. The ED₅₀ of esketamine required for children undergoing circumcision was determined by Dixon's up-and-down method, which calculated the mean of the crossover midpoints. Additionally, ED₅₀ and ED₉₅ of esketamine were estimated by probit regression. Onset time, wake-up time, vital signs including heart rate, pulse oxygen saturation and mean artery pressure, and adverse events were recorded. Differences in age, weight of the patients between the two groups were compared by one-way ANOVA. Differences in onset time, wake-up time, and vital signs including heart rate, pulse oxygen saturation (SpO₂) and mean arterial pressure in each time point between the two groups were compared by using the independent samples t-test. The ED₅₀ values of esketamine was compared between the two groups by Mann-Whitney U test. Results ·When administrated in combination with lidocaine, the ED₅₀ of esketamine for children undergoing circumcision was 1.55 mg/kg (95% CI 1.47?1.63). Compared to the data of our previous study, the ED₅₀ of esketamine required for children undergoing circumcision in combination with lidocaine was significantly lower than that of esketamine solo agent [ED₅₀ =1.90 mg/kg (95% CI 1.75?2.05)] (P=0.001). The mean arterial pressure of children pretreated with lidocaine was significantly lower than that of esketamine solo agent at each time point during the surgery (P=0.000, P=0.004, P=0.010), and no significant effect on heart rate was observed. A transient decrease in SpO₂ was observed when esketamine was used in combination with lidocaine. Conclusion ·Anesthesia induced by esketamine combined with lidocaine can significantly reduce the ED₅₀ of esketamine required for pediatric patients undergoing circumcision, and better stability of blood pressure is achieved. However, transient respiratory depression should be noted.

Objective ·To investigate the morphologic and functional changes of the diaphragm of children during early mechanical ventilation under synchronized intermittent mandatory ventilation (SIMV) mode. Methods ·Children were admitted to the Pediatric Intensive Care Unit (PICU) of Xinhua Hospital, Shanghai Jiao Tong University School of Medicineand received mechanical ventilation for at least 96 h from October 2020 to December 2021. Bedside ultrasonic testing was conducted to inspect the changes in the diaphragm at three different time points (0, 48, and 96 h, respectively). Kruskal-Wallis H test was conducted for examining the abdominal fat thickness, atrophy rate, diaphragm thickness and DE between the groups. The diaphragm thickness was further compared by Bonferroni's test for ex-post hoc comparisons. Univariate ANOVA was performed for analyzing the diaphragm contraction velocity, diaphragm thickening fraction and diaphragmatic atrophy rate between the groups. Results ·Forty-six children in PICU with complete measurement data were included. Their average age was 2.94 (1.35, 7.00) years, including 23 males and 23 females. The main disease leading to perform mechanical ventilation was pneumonia (52.17%). There was no significant difference between the choice of ventilator parameters and oxygenation status during the observation period (P>0.05). In the early stage of mechanical ventilation (within 96 h), 50% of children showed atrophy of abdominal subcutaneous fat, 36.96% showed nutritional disorders (fasting and need parenteral nutrition support), and 93.5% of children received glucocorticoid therapy. However, there was no significant difference in the atrophy degree of abdominal subcutaneous fat between the three time points (all P>0.05). Bedside ultrasonography detected significant atrophy of bilateral diaphragm thickness at three different time points (all P=0.000). After 48 h of mechanical ventilation, the atrophy rate of the right diaphragm was 4.27%±7.36%, and the left diaphragm was 3.88%±6.85%. After 96 h of ventilation, the atrophy rate of the right diaphragm was 7.69%±7.74%, and the atrophy rate of the left diaphragm came to 7.55%±7.69%. The atrophy rate of the bilateral diaphragm was significantly higher in the first 48 h of mechanical ventilation than in the 48 h to 96 h (all P =0.000). However, there were no statistically significant differences in changes of diaphragm function-related indicators (diaphragm excursion, diaphragm contraction velocity, and diaphragm thickening fraction). Conclusion ·The bedside ultrasound is a proven tool to detect diaphragmatic atrophy in mechanically ventilated children. Mechanical ventilation can induce structural atrophy of the diaphragm in children during early mechanical ventilation under SIMV mode, which is more pronounced in the first 48 h. However, the early morphological changes of the diaphragm have not affected its function.

Objective ·To obtain the evaluation tools of postoperative speech function of oral cancer in existing studies, and summarize the application methods, application scenarios and development status of the postoperative speech function assessment tools for oral cancer. Methods ·The methodological framework was based on the review method of the Joanna Briggs Institute evidence-based health care center in Australia. The databases included PubMed, Web of Science, Embase, CINAHL, CNKI, Wanfang and VIP. The English terms were ("oral cancer" or "oral cavity cancer" or "head and neck neoplasm*"[MeSH Terms]) AND ("speech" or" language" [MeSH Terms]) AND ("assess*" or "evaluat*"[MeSH Terms]), the Chinese terms were "speech", "speech disorders", "speech function", and the search discipline was limited to "stomatology" or "nursing".The retrieval time was from the establishment of the database to July 2022, and the included literature was summarized and analyzed. Results ·A preliminary search of 4 476 articles from the literature databases was obtained, excluding duplicate literature, literature that was not relevant to the purpose and content of the study, review literature, non-Chinese or non-English literature, etc. A total of 9 articles were included, including 7 cross-sectional studies and 2 cohort studies. The time range of the included literature was 1990?2022, and the national sources included the United States, Japan, Germany, India, etc. A total of three evaluation methods were summarized, namely scales, automatic identification technology and other methods such as internet of things (IoT) devices, in which scale evaluation is currently the most mainstream evaluation method, and speech handicap index (SHI) is one of the most widely used evaluation scales, which has been culturally adapted and localized in China, but the evaluation tools of local original research have not been retrieved. Conclusion ·Among the oral cancer postoperative speech assessment tools, the scale is the most widely used method, but there are few studies that can balance subjective speech assessment and objective speech assessment, and the domestic related research is vacant. In the future, relevant research can be carried out in combination with these two aspects, and a tool for assessing speech function after oral cancer surgery suitable for local languages can be developed.

Objective ·To develop a knowledge, attitude, belief and practice (KABP) scale for safe medication in patients with chronic kidney disease (CKD), and test its reliability and validity. Methods ·Based on the KABP theory, the initial items were discussed and designed comprehensively by research group members through a systematic literature review and semi-structured interviews. The Delphi method of expert panel consultation and the pre-investigation were conducted to improve the initial scale. Next, the patients with CKD in Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine were enrolled to complete the initial scale. The item analysis was conducted by critical ratio and homogeneity test. The construct validity and the content validity of scale were tested by exploratory factor analysis (EFA) and logic analysis, respectively. The reliability of the scale was evaluated by Cronbach's α coefficient, split-half reliability, and test-retest reliability. Results ·The initial scale consisted of 29 items with three dimensions. A total of 213 questionnaires were distributed and 209 valid questionnaires were collected. Items No.1, 2, 3 and 19, which did not meet the criteria of three or more indicators, were deleted after item analysis. The KMO (Kaiser-Meyer-Olkin) was 0.946, and the χ² value of Bartlett's spherical test was 4 554.451 (P=0.000). The results suggested that the overall correlation matrix had common factors, which was suitable for factor analysis. The principal component analysis and the maximum variation method of orthogonal rotation axis were adopted. Item No.13 was deleted finally. According to the variable characteristics contained in each factor, three extracted common factors were named as "Practice of safe medication", "Knowledge about safe medication", and "Belief of safe medication", respectively. The eigenvalues of three dimensions were 6.565, 6.176, and 3.863, respectively, and the cumulative variance contribution rate was 69.18%. The scale-level-content validity index (S-CVI)/universal agreement was 0.860. The S-CVI/average was 0.987. The formal scale was formed of 24 items with three dimensions. The α coefficient of the total scale was 0.964. The split-half reliability coefficient was 0.911 and the test-retest reliability was 0.892 for the scale. Conclusion ·The KABP scale of safe medication in CKD patients has good reliability and validity.

Objective ·To investigate the dietary intake of n-3 polyunsaturated fatty acids (n-3 PUFA),including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), and serum mercury levels in the pregnant women in Shanghai, and analyze whether n-3 polyunsaturated fatty acids intake and mercury exposure are risk factors of GDM. Methods ·From January 2018 to January 2021, dietary survey, clinical data collection, and serum samples collection and testing were conducted among the pregnant women who sought prenatal care in Shanghai Seventh People's Hospital, Shanghai University of Traditional Chinese Medicine. Dietary and dietary supplements were investigated by semi-quantitative food frequency questionnaire at 24^±1 gestational week. The n-3 PUFA intake (dietary DHA and EPA, and DHA supplements) and serum mercury in control group were divided into tertiles. After adjusting the other known risk factors for GDM (BMI, age, family history of diabetes, and energy), the odds ratios and 95% confidence intervals of the risk of GDM were calculated by Logistic regression. Partial correlation analysis was used to analyze the correlation between dietary DHA or EPA and serum mercury. Results ·Among 519 pregnant women, there were 361 normal pregnant women and 158 pregnant women with GDM. The average intakes of DHA and EPA in the normal pregnant women were 29.78 mg/d and 23.90 mg/d, respectively and the average intakes of DHA and EPA in the pregnant women with GDM were 37.47 mg/d and 28.94 mg/d, respectively. All of them were far below the appropriate intake recommended by the Chinese Nutrition Society. The mean value of serum mercury was 0.31 μg/L in the normal pregnant women and 0.29 μg/L in the pregnant women with GDM. After adjusting the other risk factors, multivariate Logistic regression analysis showed that dietary DHA intake (P trend=0.135), dietary + supplement DHA (P trend=0.371), EPA intake (P trend=0.106), dietary intake of n-3 PUFA (P trend=0.382) and serum mercury (P trend=0.514) were not significantly correlated with GDM. The partial correlation analysis found that dietary DHA and dietary EPA were not significantly correlated with serum mercury in the pregnant women (P=0.126, P=0.543). Conclusion ·Low level of n-3 PUFA intake and mercury exposure are not associated with GDM.

Coronavirus disease 2019 (COVID-19) has become a major global public health event as a new acute respiratory infectious disease. During the COVID-19 pandemic, compared with the healthy population, cancer patients had a higher risk of developing comorbidities of other systems, due to their bad poor immunity and older age. Research showed that breast cancer, as a malignant disease, had the highest disease incidence in female patients. Breast cancer patients with COVID-19 infection often have worse prognosis, and they have to postpone anti-tumor treatment due to COVID-19 infection. At present, the effect of delayed treatment on the survival rate of breast cancer patients is unclear, and whether the treatment plan of these patients should be adjusted is still being studied. Through the systematic review of existing clinical research studies, the guidelines of various societies and the expert consensus, this paper reviews the selection and rationalization of breast cancer treatment options under the COVID-19 epidemic, and discusses the opportunity and approaches of anti-tumor treatment for breast cancer patients infected with COVID-19.

With the rapid advances in nanotechnology and materials science, lots of nanomaterials designed and modified according to the pathophysiological and chemical properties of the disease microenvironment have been proven to achieve effective therapeutic effects by triggering in situ catalytic reactions through specific stimuli. However, in response to the structural complexity and potential metal ion toxicity of current catalysts for nanomedical applications, researchers have worked to develop and improve the synthesis of nanocatalysts which are significantly more effective, more controllable and less toxic. In recent years, single-atom catalysts (SACs) show great potential for therapeutic applications as atomically dispersed metal active sites, anchored or coordinated on suitable carriers with excellent catalytic activity and high selectivity. This review provides an outline of the progress in development of SACs for biomedical applications, focusing on recent advances in applications encompassing antimicrobial, cancer therapy, oxidative-stress cytoprotection and biosensing, and revealing the catalytic triggering mechanisms of SACs for different disease applications by citing a series of successfully established representative examples and understanding the structure-property relationships. Finally, current challenges and future perspectives for the engineering of SACs in noncatalytic medicine are also discussed and outlooked.

Klebsiella pneumoniae (Kp)is widely distributed in nature. Pathogenic Kp can cause a wide range of clinical infections, including respiratory infection, bloodstream infection, liver abscess, urinary system infection and so on. As a famous "plasmid collector", Kp can habor different types of plasmids in its genome. As a result, multidrug-resistant (MDR) strains continue to appear in recent years. Especially, the emergence of hypervirulent MDR (hv-MDR) Kp brings great challenges to clinical treatment. Therefore, the ability of Kp to obtain foreign genes, especially drug resistance and virulence-related genes, has attracted the attention of a large number of scholars. As the major acquired immune system in bacteria, the active clustered regularly interspaced palindromic repeats/CRISPR-associated proteins (CRISPR-Cas) system can effectively block the horizontal transfer of mobile elements into the genome of Kp, especially for transfer ability of conjugative plasmids. In recent years, it has been found that some conjugative plasmids carry anti-CRISPR (Acr) protein to inhibit the activity of the CRISPR-Cas system encoded by host bacteria, escape the host immune recognition, and then can effectively transfer between hosts. The sequenced Kp genome showed that the main types of CRISPR-Cas system in its genome were type I-E and subtype I-E^*. Therefore, analysis of the relationship between the CRISPR-Cas distribution and transfer ability of plasmid in Kp and further exploration of the mechanism of Acr protein in regulating the activity of CRISPR-Cas, will provide clues and direction to the dynamics of its genome evolution. It will eventually provide clinical guidance for the prevention and control of hv-MDR Kp.

Lung cancer is one of the most serious health problems worldwide, and it is crucial to accurately diagnose its severity and staging, assess treatment response and prognosis, and develop new treatment strategies. In recent years, lipidomics has emerged as a new hotspot that focuses on understanding disease-related lipid metabolism, discovering biomarkers and monitoring targets for therapeutic strategies, and providing insights into the lipid profile and pathophysiological mechanisms of lung cancer. Disorders of lipid metabolism are a series of abnormalities in lipid metabolism caused by structural and functional alterations of some genes in tumor cells, which affect cellular functions such as cell cycle, proliferation, growth and differentiation, leading to carcinogenesis. In addition, the specificity of lipid metabolism can be used to identify new metabolic targets for lung cancer treatment, and in clinical practice, lipid-lowering drugs and anti-lipid peroxidation therapy are effective. This article reviews the latest research advances in lipid metabolism in the development, progression, diagnosis, and treatment of lung cancer, focusing on the novel mechanisms by which disorders of lipid metabolism support the growth of lung cancer and the potential targets of lipid metabolism, discusses therapeutic approaches to target lipid metabolic pathways in lung cancer, and presents the future prospects and challenges of lipidomics in lung cancer.

Insecticide is one of the main categories of pesticides used in agriculture and households, including organo-chlorine pesticide (OCP), organophosphate pesticide (OP), carbamate pesticide (CM), pyrethroid pesticide (PYR), and neonicotinoids. They are widely used for pest control in agricultural gardens and homes. The residues of insecticides have been extensively detected in the environment, and they can be enriched through multiple exposure pathways (such as drinking water, food chain) to produce adverse health effects on humans. In recent years, the potential reproductive health risk to females has attracted people's attention. There is an increasing evidence that insecticide exposure is related to female reproductive endocrine abnormalities, menstrual cycle disorders, decreased fertility, long time to pregnancy, spontaneous abortion and female internal genital diseases. However, the mechanism of the impact of pesticides on female reproductive health remains unclear. This article reviews recent epidemiological studies on the relationship between insecticides exposure and female reproductive health. This article also discusses the potential effects of insecticides on the interference of hypothalamus-pituitary-gonadal axis, oxidative stress, and germ cell apoptosis.

Root canal irrigation is essential to disinfect the main root canal, the root canal isthmus, and the lateral root canals. Traditional syringe irrigation is the most widely used irrigation method. Due to the intricate three-dimensional structure of the root canal system, the fluid cannot penetrate all areas. Therefore, syringe irrigation does not flush out tissue residues and dentin debris well. This accumulated hard tissue debris may interfere with the sealing properties of the root canal filling material and hinder disinfection. Laser-activated irrigation has emerged as an effective root canal irrigation technique. The new Er:YAG laser swabbing mode has greatly improved the efficiency of removing debris and medication from root canals.This article summarizes the effectiveness and advantages of Er:YAG laser in root canal irrigation and the current status of the application of Er:YAG laser to root canal treatment.